Psychopharmacology (Berl). 2004 Apr;173(1-2):175-85. Epub 2004 Jan 15.
Effects of acute and chronic buspirone on impulsive choice and efflux of 5-HT and dopamine in hippocampus, nucleus accumbens and prefrontal cortex.

Liu YP, Wilkinson LS, Robbins TW.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

RATIONALE. Reduced central serotonin (5-HT) activity has been associated with impulsive choice behaviour, but there is no consensus about the precise nature of these effects. Behavioural and neurochemical effects of 5-HT(1A) agonists such as buspirone depend critically on the dose and the duration of treatment. We thus undertook a parametric study of the effects of acute and chronic buspirone on the performance on a test of delayed gratification, as well as on the efflux of serotonin and dopamine (DA) in cortical and subcortical regions in rats. OBJECTIVES. Three experiments examined (i) the effects of acute buspirone on impulsive choice and how such effects were modified by prior chronic exposure to buspirone; (ii) the effects of chronic buspirone on impulsive choice; (iii) the effects on impulsive choice of a selective 5-HT(1A) antagonist, WAY-100635 tested alone and in combination with buspirone; (iv) the effects of chronic and acute buspirone on 5-HT and DA efflux in anaesthetised rats. METHODS. In experiment 1, rats previously trained on the delayed gratification task were tested with acute buspirone (0.5, 1 and 2 mg/kg). The same rats were then treated with chronic buspirone (1 mg/kg/day) over the next 65 days, and the effects of acute buspirone (1 mg/kg) re-determined at 20, 45 and 65 days of chronic treatment. In experiment 2, two groups of rats trained on the delayed gratification task were treated either with saline or buspirone (1 mg/kg/day) continually for 65 days before being tested with acute buspirone (1 mg/kg), WAY-100635 (0.08 mg/kg), or a combination of the two drugs. In experiment 3, rats received the same regimen of buspirone dosing as in experiment 2, before receiving in-vivo microdialys

kobepharma-u.ac.jp

Effects of the serotonergic anxiolytic buspirone on plasma glucose and glucose-induced hyperglycemia were studied in mice. Buspirone did not affect plasma glucose levels of non-fasted mice, while it increased serum insulin levels. In fasted mice, buspirone significantly reduced glucose-induced hyperglycemia and enhanced insulin release elicited by glucose. This suggests that buspirone enhances insulin release, resulting in inhibition of glucose-induced hyperglycemia. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) increased serum insulin levels and induced a slight hypoglycemia in non-fasted mice. 1-PP decreases glucose-induced hyperglycemia and amplifies insulin release elicited by glucose in fasted mice. Since buspirone is mainly metabolized to 1-PP and formation of 1-PP occurs quickly, the inhibitory effect of buspirone on glucose-induced hyperglycemia is likely mediated by 1-PP.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14737015&dopt=Abstract buspirone Buspar




Psychopharmacology (Berl). 2004 Feb 4 [Epub ahead of print]
Social instability in female rats: effects on anxiety and buspirone efficacy.

Haller J, Baranyi J, Bakos N, Halasz J.

Institute of Experimental Medicine, PO Box 67, 1450, Budapest, Hungary.

RATIONALE. Buspirone produces inconsistent effects in laboratory rodents. Individual housing increases the efficacy of buspirone in male rats, suggesting that the effects of this (and other) compounds become conspicuous in animals showing anxiety-like states. The effect of individual housing was, however, weak, and evident only when the locomotor suppressive effects of buspirone dissipated (i.e. 4 h after treatment). OBJECTIVES. The effects of social instability, a recently developed model of social stress in female rats, was investigated on both anxiety and the anxiolytic efficacy of buspirone. METHODS. Female rats were exposed to alternate days of isolation and moderate crowding for 2 weeks. Group composition was changed for each crowding phase. Basal anxiety and the anxiolytic efficacy of buspirone were assessed by the social interaction test of anxiety 24 h after the last crowding phase. RESULTS. Crowding appeared stressful, as it increased plasma glucocorticoid levels in less than 1 h. Anxiety-like behaviours were increased by social instability compared with stable group housing. In group housed controls, buspirone markedly suppressed locomotion, without clear effects on anxiety-related behaviours. Social instability attenuated the locomotor suppressive effects of buspirone, but made the anxiolytic effects of the compound more conspicuous. The effects of individual housing (assessed earlier) and social instability (assessed here) on buspirone efficacy appear qualitatively different. CONCLUSIONS. Buspirone abolishes stress-induced anxiety, but has no anxiolytic effects in controls. This is consistent with clinical findings, as the drug decreases anxiety in anxious patients but not in healthy humans. Laboratory models involving stress-induced anxiety-like state

vetmed.wsu.edu

A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzyme-linked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14765730&dopt=Abstract buspirone Buspar

musc.edu

Anxiety symptoms are common among opioid-dependent individuals. Buspirone, a nonbenzodiazepine anxiolytic, has been used successfully for the treatment of anxiety in alcoholic patients. Its efficacy in opioid-dependent patients has not been previously examined. We conducted a twelve-week, randomized, placebo-controlled trial of buspirone in 36 subjects receiving methadone-maintenance treatment who presented with anxiety symptoms. Measures of anxiety, depression, and substance use were obtained repeatedly during treatment. Buspirone treatment did not significantly reduce anxiety symptoms in opioid-dependent patients. However, buspirone treatment was associated with trends toward reduction in depression scale scores and a slower return to substance use.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14766438&dopt=Abstract buspirone Buspar




J Pharmacol Exp Ther. 2004 Feb 9 [Epub ahead of print]
Buspirone Raises Blood Pressure through Activation of Sympathetic Nervous System and by Direct Activation of {alpha}1-adrenergic Receptors Following Severe Hemorrhage.

Osei-Owusu P, Scrogin KE.

Stritch School of Medicine.

Serotonin 5-HT1A receptor agonists reverse the hypotensive and sympathoinhibitory responses to severe hemorrhage in rats. To determine if 5-HT1A receptor-mediated pressor responses in hypovolemic animals are due to sympathoexcitation and/or direct vasoconstriction, blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to the partial 5-HT1A receptor agonist, buspirone, or the more selective, full 5-HT1A-receptor agonist (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were compared in intact and ganglionic blocked, hemorrhaged Sprague-Dawley rats. Buspirone produced dose-dependent increases in BP (110 +/- 4**, 86+/-4**, 65+/-7 mmHg), HR (369 +/- 10**, 337+/-14, 277+/-16 bpm) and RSNA (114 +/-36**, 34+/-21, -23+/-25 %Baseline for 0.2, 0.1 and 0 mg/kg, **p<0.01 vs. 0 mg/kg 3 min after injection). Ganglionic blockade with hexamethonium chloride blocked the pressor effect of 9.9 micro g/kg 8-OH-DPAT and attenuated, but did not block, the pressor response to 0.2 mg/kg Bus (85+/-7 vs. 46+/-6 mmHg for buspirone + ganglionic blockade vs. saline + ganglionic blockade; p<0.01). In subsequent tests, rats treated with the selective alpha1-adrenergic receptor antagonist, prazosin (25 micro g/kg), continued to show extensive tachycardic (+73+/-26 bpm) and sympathoexcitatory (128+/-55 % baseline) responses to 0.2 mg/kg buspirone. Ganglionic blockade combined with prazosin completely blocked all responses to buspirone. Buspirone (0.2 mg/kg) produced significant bradycardic (-89+/-12 bpm, p<0.01) and sympathoinhibitory (-72+/-7 %baseline, p<0.01) responses in euvolemic rats 3 min after injection. It is concluded that the pressor effect of buspirone is unique to hypovolemic animals and, is mediated




J Pharm Biomed Anal. 2004 Apr 1;35(1):9-19.
The photocatalytic process as a tool to identify metabolitic products formed from dopant substances: the case of buspirone.

Calza P, Pazzi M, Medana C, Baiocchi C, Pelizzetti E.

Dipartimento di Chimica Analitica, Universita di Torino, via P. Giuria 5, 10125 Torino, Italy.

The photocatalytic transformation of buspirone, an analgesic anxiolytic drug, and the formation of intermediates products have been evaluated by adopting titanium dioxide as a photocatalyst. Several molecules resulting from buspirone degradation have been identified and characterized by using HPLC/MS/MS technique. The main intermediates formed in these experimental conditions agree with the major buspirone metabolites found "in vivo" on rats and horses: hydroxy and dihydroxy-buspirone, despyrimidinyl buspirone and 1-pyrimidinyl piperazine. This shows that the photocatalytic system could provide in the present case a useful simulation of the metabolic transformation of dopant substances. Moreover, some more oxidized species have been recognized with the photocatalytic process, and this could offer a suggestion for yet to come metabolism studies.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15030875&dopt=Abstract buspirone Buspar

byk.gulden.de

The affinity for functional alpha1-adrenoceptor subtypes of buspirone in comparison with its close structural analogs and selective alpha1D-adrenoceptor antagonists, BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]dec ane-7,9-dione) and MDL 73005EF (8-[2-(1,4-benzodioxan-2-ylmethylamino)ethyl]-8-azaspiro+ ++[4.5]decane-7,9-dione), was determined, namely at subtype A in rat vas deferens and perfused kidney, at subtype B in guinea-pig and mouse spleen, at subtype L in rabbit spleen, and at subtype D in rat aorta and pulmonary artery against noradrenaline-evoked contractions. BMY 7378 and MDL 73005EF were confirmed as 30- and 20-fold selective antagonists, respectively, for alpha1D- over both alpha1A- and alpha1B-adrenoceptors. Buspirone was a weak antagonist without intrinsic activity at alpha1A-adrenoceptors in rat vas deferens (pA2 = 6.12), at alpha1B-adrenoceptors in guinea-pig and mouse spleen (pA2 = 5.54 and 5.59) and at alpha1L-adrenoceptors in rabbit spleen (pA2 = 4.99), but caused partial vasoconstriction in rat kidney that was attenuable by the subtype D-selective adrenoceptor antagonist BMY 7378, but hardly by the subtype A-selective adrenoceptor antagonist B8805-033 ((+/-)-1,3,5-trimethyl-6-[[3-[4-((2,3-dihydro-2-hydroxymethyl)-1,4-be nzodioxin-5-yl)-1-piperazinyl]propyl]amino]-2,4(1H,3H)-pyrimidinedion e), confirming the additional presence of alpha1D-adrenoceptors mediating rat renal vasoconstriction. Buspirone behaved as a partial agonist at alpha1D-adrenoceptors in rat aorta (pD2 = 6.77, intrinsic activity (i.a.)= 0.40) and pulmonary artery (pD2 = 7.16, i.a. = 0.59). With buspirone as agonist in these tissues, the pA2 values of subtype-discriminating antagonists were consistent with their alpha1D-adrenoc